Inducible nitric oxide synthase is an endogenous neuroprotectant after traumatic brain injury in rats and mice

Elizabeth H. Sinz, Patrick M. Kochanek, C. Edward Dixon, Robert S B Clark, Joseph A. Carcillo, Simon C. Watkins, Joanne Schiding, Timothy M. Carlos, Timothy R. Billiar

Research output: Contribution to journalArticlepeer-review


Introduction: Inducible nitric oxide synthase (iNOS) is upregulated by cytokines and is detected in brain during the acute inflammatory response to traumatic brain injury (TBI).1 In sepsis models, iNOS-derived nitric oxide (NO) prevents apoptosis in hepatocytes2 while in stroke, it is detrimental.3 We studied the role of iNOS in TBI using two methods; 1) treatment of rats with iNOS inhibitors aminoguanidine (AG) or N-iminoethyl-D-lysine (NIL), and 2) assessment of knockout mice lacking the gene for iNOS (knockout, -/-). Methods: Male Sprague-Dawley rats (n=10/grp), underwent controlled cortical impact (CCI) with secondary hypoxemia (FiO2 = 0.11 for 30 min).4 After injury, Alzet pumps were implanted SQ to deliver AG (∼180 mg/kg/d), NIL (∼60 mg/kg/d) or saline vehicle. In male mice (n=8/grp), CCI was performed in iNOS (-/-) and wild type (+/+) littermates. Outcome parameters included motor function and memory acquisition (Morris water maze [MWM], as well as histology (contusion volume and hippocampal neuron counts). Results: In rats, treatment with AG or NIL exacerbated damage in CA1 and CA3 (p < 0.05 vs vehicle) but did not expand the contusion. iNOS (/-) mice showed markedly increased latency in MWM (p < 0.05 vs +/+) after CCI. Conclusion: An endogenous neuroprotectant role for iNOS-derived nitric oxide after TBI is strongly supported.

Original languageEnglish (US)
Pages (from-to)A36
JournalCritical care medicine
Issue number1 SUPPL.
StatePublished - 1998

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine


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